Platelet-activating factor (PAF), a proinflammatory lipid mediator, plays a crucial role in the formation of the atherosclerotic plaque. Therefore, the inhibition of endothelium inflammation by nutraceuticals, such as PAF inhibitors, is a promising alternative for preventing cardiovascular diseases. The aim of the present study was to evaluate the impact of a new functional yogurt enriched with PAF inhibitors of natural origin from olive oil by-products on PAF metabolism. Ninety-two apparently healthy, but mainly overweight volunteers (35–65 years) were randomly allocated into three groups by block-randomization. The activities of PAF’s biosynthetic and catabolic enzymes were measured, specifically two isoforms of acetyl-CoA:lyso-PAF acetyltransferase (LPCATs), cytidine 5′-diphospho-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-CPT) and two isoforms of platelet activating factor acetylhydrolase in leucocytes (PAF-AH) and plasma (lipoprotein associated phospholipase-A2, LpPLA2). The intake of the enriched yogurt resulted in reduced PAF-CPT and LpPLA2 activities. No difference was observed in the activities of the two isoforms of lyso PAF-AT. In conclusion, intake of yogurt enriched in PAF inhibitors could favorably modulate PAF biosynthetic and catabolic pathways.
Inflammation, thrombosis and oxidative stress are rarely studied together when wine’s biological activity is concerned; hence the existing literature lacks a holistic point of view in the biological outcome. The scope of the present study is to parallel evaluate the effect of wine extracts on those mechanisms. Ten wine varieties and two different extraction methods were used leading to five extracts for each wine: total lipids (TL) and fractions with different phenolic compound classes (FI, FII, FIII and FIV). Their effect on oxidative stress, platelet aggregation and the secretion of cytokines from mononuclear cells was measured and a biological score was calculated. FII of white wines is the most potent extract and the extracts FIII and TL are following. Specifically, FII had higher anti-oxidant and anti-inflammatory score while all three fractions had a similar anti-platelet score. Furthermore, FII and FIII extracts were the most potent red wine extracts and revealed the highest anti-oxidant and anti-inflammatory scores. White wine FII extracts were more potent than the red wine ones while FI and FIV extracts of red wine were more potent than the white wine ones. In conclusion, the protective effect of a wine is independent of its color but is strongly associated with its microconstituents profile. FII extract revealed the highest biological score and further examination is needed in order to identify the compounds that are responsible for the aforementioned actions.
Platelet-activating factor (PAF) is a potent lipid mediator, involved in thrombosis, inflammation, and atherosclerosis. The protective effect of wine and olive oil against atherosclerotic diseases is largely attributed to their phenolic compounds and mostly to resveratrol and tyrosol. Both compounds have been reported to inhibit PAF biosynthesis in interleukin-1β (IL-1β)-stimulated monocytes and also to attenuate PAF biosynthesis in cell lysates. The aim of this study was to investigate the effects of resveratrol, tyrosol, and their derivatives on unstimulated U937 cells and to explore the intracellular messaging pathways that participate in the activation of PAF biosynthesis in the same cell line. Tyrosol and its derivatives did not exert any substantial effect on PAF biosynthesis. Resveratrol (50 and 100 μM), as well as its methoxy derivative (5–20 μM), caused a reduction in the PAF biosynthetic enzymes’ activity by 20–43% after 24 h of incubation. On the other hand, lower resveratrol concentration (10 μM) and higher concentration of the methoxy derivative (50 μM) increased the Ca2+-dependent lyso–PAF acetyltransferase (LysoPAF-ATC) activity by 28–45% after half-hour incubation via p38 mitogen-activated protein kinase (p38-MAPK) action. IL-1β activated PAF biosynthetic pathways via different signaling pathways, with phospholipase C-β (PLC-β) being a key enzyme.
A fish-rich diet has a beneficial effect on cardiovascular health. The platelet activating factor (PAF) is involved in the development of atherosclerosis, and in vitro results support the regulating action of bioactive nutrients on PAF metabolism. The purpose of this study is to examine whether the consumption of farmed fish fed with an olive-pomace enriched diet (EF) affects PAF metabolism and the markers of inflammation and oxidative stress compared to the consumption of conventionally fed farmed fish (CF). Thirty apparently healthy adults completed a randomized double-blind crossover trial, during which they consumed both CF and EF twice a week for 8 weeks with a six-week washout period in between. The activities of PAF acetylhydrolase (PAF-AH), lysoPAF acetyltransferase (lysoPAF-AT), DTT-insensitive CDP-choline: 1-alkyl-2-acetyl-sn-glycerol-choline-phosphotransferase (PAF-CPT) in leukocytes, and lipoprotein-associated phospholipase A2 (LpPLA2) in serum were determined. The quantities of interleukin-6 (IL-6), high sensitivity C-reactive protein (hsCRP), oxidized LDL (ox-LDL), thiobarbituric acid-reactive substances (TBARS), and glutathione peroxidase (GPx), as well as the serum oxidation, were also determined. Both types of fish exerted similar effects as there were no statistically significant differences between the two interventions except for an elevated PAF-CPT and reduced arachidonic acid (AA) in the red blood cell (RBC) membrane lipids after the EF intake.
Objective: The effect of the daily consumption of a low-fat yogurt (150 g) enriched with Platelet-Activating Factor receptor (PAF-R) antagonists, or the plain one, on gut microbiota and faecal metabolites was investigated in healthy overweight subjects. Methods: A randomized, three-arm, double-blind, placebo-controlled, parallel-group study was performed that lasted 8 weeks. Blood and stools were collected and analyzed before and after the intervention. Results: Our findings revealed that the intake of the enriched yogurt resulted in a significant increase in the levels of Bifidobacterium spp., Clostridium perfringens group and Firmicutes-to-Bacteroidetes (F/B) ratio. On the other hand, a significant increase in the levels of Lactobacillus and C. perfringens group was detected after the intake of the plain yogurt. The increase in the levels of C. perfringens group was inversely associated with the plasma catabolic enzyme of PAF, namely LpPLA2 (lipoprotein-associated phospholipase A2), a cardiovascular risk marker that has been linked with inflammation and atherosclerosis. Moreover, in the enriched with PAF-R antagonists yogurt group, the increased levels of C. perfringens group were also associated with lower PAF action assessed as ex vivo human platelet-rich plasma (PRP) aggregation. Additionally, a higher % increase in molar ratio of Branched Short Chain Fatty Acids (BSCFAs) was detected for both yogurt groups after the 8 week-intervention compared to control. The consumption of the enriched yogurt also resulted in a significant drop in faecal caproic levels and a trend for lower ratio of butyrate to total volatile fatty acids (VFAs) compared to baseline levels. Conclusion: Yogurt consumption seems to favorably affect gut microbiota while its enrichment with PAF-R antagonists from olive oil by-products, may provide further benefits in healthy overweight subjects. Clinical Trial Registration: ClinicalTrials.gov (NCT02259205).